Qualitative researchers have long recognized that fatigue is a common concern among those with chronic illness; however, the insights derived from this body of inquiry have not been synthesized into a coherent body of clinical knowledge that could provide direction for nursing practice. Using a synthesis approach of meta-study, the authors identify four predominant assumptions embedded in qualitative studies that have influenced the way researchers have interpreted and made sense of their findings about fatigue in chronic illness over the past two decades. They argue that these assumptions may have inhibited the development of more dynamic, comprehensive understandings of fatigue. They conclude that addressing some of the methodological issues within this body of research might lead to a more accurate portrayal of the complexity, fluidity, and contextual nature of the fatigue experienced in chronic illness.